Archives of Pharmacy

Microglial Dysfunction and Cognitive Impairment in Animal Models of Type 2 Diabetes: A Systematic Review Bridging Diabetes and Early-Stage Neurodegeneration

Jovana Aranđelović Ilić — 2026-04-29

Type 2 diabetes (T2D) is closely associated with cognitive impairment and an increased risk of dementia. Early neuropathological alterations in T2D are increasingly considered to involve neuroinflammatory processes, suggesting that microglial function in the diabetic brain may be compromised or shifted towards a maladaptive activated state. Growing evidence implicates microglial dysfunction as a key mechanism underlying T2D-related cognitive impairment. Alterations in spatial learning, memory, and executive function are accompanied by functional and phenotypic changes in microglial cells, particularly within hippocampal and cortical circuits. At the same time, early neurodegenerative changes occur, including neuronal loss, synaptic alterations, accumulation of Aβ and p-Tau, and Alzheimer’s disease (AD)-related transcriptomic signatures in vulnerable brain regions. With aging, microglia contribute more significantly to neurodegeneration as their regulatory interactions with neurons weaken, favoring sustained activation. This mini systematic review aims to synthesize current in vivo evidence on the relationship between cognitive impairment and microglial alterations in animal models of T2D and to delineate the underlying pathophysiological mechanisms linking chronic metabolic stress, microglial dysfunction, and early neurodegenerative changes. Furthermore, it seeks to highlight how these mechanistic pathways, encompassing microglial signaling, inflammatory mediators and metabolic reprogramming, may represent promising therapeutic targets for preventing or attenuating diabetes-associated neurodegeneration.

Pharmacists’ Knowledge and Attitudes Regarding Biologics and Biosimilars: A Literature Review

Marija Trajculeski — 2026-04-29

Advancements in biologic therapies have become crucial for managing both acute and chronic illnesses. In addition, the growing presence of biosimilar medications presents significant opportunities for reducing healthcare costs and expanding patient access to essential biologic treatments. Pharmacists, as part of the healthcare system, play an important role in the use of this group of medications. The purpose of this literature review is to examine existing research on pharmacists’ knowledge and attitudes toward originator biologics and biosimilars, as well as assessing the need for further educational initiatives in this area.

A digital search of literature was carried out through journal databases, such as PubMed, and Scopus, using selected search terms, and applying the inclusion criteria that match the aim of the research. The majority of studies that are subject to evaluation have been conducted, in the form of short surveys, revealing that most of the pharmacists are familiar with the biologic and biosimilar medicines, however their measured knowledge was less extensive than their self-assessed knowledge. Pharmacists’ knowledge and attitudes towards biologics exhibit a wide variation. Insufficient clinical experience and need for additional education were identified as prerequisites for greater inclusion of biologic originator and biosimilar medicines in clinical practice.

Development and Validation of an RP-HPLC Method for the Determination of Tiazotic Acid and Its Impurity with Application to Tablet Analysis

Branka Ivković — 2026-04-29

A simple and precise RP-HPLC method was developed and validated for the determination of tiazotic acid and its impurity, 3-methyl-1,2,4-triazole-5-thione, with application to tablet analysis. Chromatographic analysis was performed using a Hypersil GOLD aQ C18 column (150 × 4 mm, 3 µm) under isocratic elution conditions with a mobile phase consisting of phosphate buffer (pH 3.3) and methanol in a ratio of 99:1 (v/v), at a flow rate of 1 mL/min and a column temperature of 30 °C. Detection was carried out at 220 nm. The developed method was validated in accordance with ICH guidelines. The following analytical parameters were evaluated during validation: selectivity, linearity, precision, accuracy, robustness, and the limit of quantification (LOQ) for the investigated impurity. The method demonstrated linearity over the concentration range of 0.139–0.238 mg/mL (r = 0.9992) for tiazotic acid and 0.091–1.56 µg/mL (r = 0.9998) for the impurity. Good precision (RSD < 2% for tiazotic acid and RSD < 10% for the impurity), accuracy (recovery in the range of 98–102% and 70–130% for the impurity), and robustness were confirmed. The impurity 3-methyl-1,2,4-triazole-5-thione was detected in tiazotic acid tablets; however, its content was below the limit of quantification (LOQ) of the proposed method (0.091 µg/mL).

Sex-specific Associations Between Serum Quinolinic Acid and Disease Severity in Relapsing-remitting Multiple Sclerosis: A Cross-sectional Study

Marija Vasić — 2026-04-29

The kynurenine pathway (KP) of tryptophan metabolism generates metabolites with both neuroprotective and neurotoxic properties and has been implicated in multiple sclerosis (MS). However, the relationship between KP metabolites, disease severity, and sex remains unclear. Serum levels of quinolinic acid (QA) and kynurenic acid (KA) were analyzed in a cohort of patients with relapsing-remitting MS. Of the 78 initially recruited patients, biomarker data were available for 40 patients, who were included in the final analysis. Disease severity was assessed using the Multiple Sclerosis Severity Score (MSSS) and patients were stratified into mild-to-moderate (MSSS < 6.7) and a severe disease group. Serum QA and KA concentrations were measured by the enzyme-linked immunosorbent assay (ELISA) and analyzed using two-way ANOVA with Sidak post hoc correction. No significant overall sex-related differences in serum QA or KA levels were observed. KA levels did not differ across MSSS categories. Female patients with high disease severity (MSSS > 6.7) exhibited higher serum QA levels compared with those with lower disease severity (p = 0.032), although this finding was observed in a very small subgroup of female patients (n = 3). These findings suggest a possible sex-related association between elevated serum QA levels and greater disease severity in female patients with RRMS and warrant confirmation in larger studies.